Prior to the late 1960's medical instruments were sterilized by autoclaving, by liquid sterilization systems such as glutaraldehyde, or by use of ethylene oxide. In the late sixties and early seventies sterilization systems involving aerosols of less obnoxious sterilants were proposed, and machines employing aerosol systems were developed for use in the packaging industry. However aerosols were not able to meet the requirements for sterilizing medical instruments and particularly were unsuccessful in treating lumens and occluded or mated surfaces. Consequently aerosol systems soon gave way to vapour and plasma based systems which were shown to be faster and more effective for sterilizing mated surfaces, lumens and occluded surfaces, although liquid phase systems continued to be used.
Chemical sterilizing systems may thus be broadly classified into three categories:
(1) Liquid systems employing a biocidal agent in the liquid phase,
(2) Aerosol systems in which a biocidal agent in a liquid phase is employed as a finely divided suspension of droplets in a gas, and
(3) Vapour systems employing the agent in a gaseous, plasma, or vapour phase,
The third (vapour) category may be further subdivided into systems employing the gas or vapour at atmospheric pressure or above, and those (including gas plasmas) which operate at sub-atmospheric pressure.
Each of the above categories of process has had disadvantages for treating medical instruments. The inadequacies of known techniques for sterilization become particularly evident when attempts are made to sterilize an endoscope. Endoscopes have narrow lumens of small diameter, for example 1 mm, and may be more than 2.0 meters in length. Many of their parts such as the control head include mated surfaces, or occluded surfaces. Their construction incorporates heat sensitive materials and they should not be heated above about 70° C. It would be desirable to be able to sterilize an endoscope, and have it immediately ready for use (i.e. sterile, dry, and at below 45° C.), in the time that it takes to conduct an endoscopic procedure, say within about 20 minutes. Because endoscopes cannot be sterilized in the time that it takes to perform a procedure, a large amount of capital is tied up in additional endoscopes consequently required.
Prior to the present invention it has not been possible to present a sterilised, dry, safe endoscope, ready for reuse in less than about 20 minutes. Also prior art liquid processes have either used external rinse water, with an attendant risk of infection, or require sterile rinse water, while vapour systems require a vacuum system with attendant disadvantages.
Similar problems to those experienced with endoscopes arise when attempting to sterilize mated surfaces, such as occur in many medical instruments, for example those having threaded parts, and also at the point of support of instruments in a sterilization chamber. Unless the sterilizing agent can penetrate mated surfaces, that part of the surface which is supported in the sterilizer may harbour micro-organisms and the instrument will not be sterile. This can only be avoided by shifting the points of support but at the cost of doubling the treatment time and added complexity.
Although the present invention is an improved aerosol system, the process has advantages over prior art liquid and prior art vapour sterilization systems and consequently each of those systems will also be briefly reviewed.
Liquid Sterilizing Agents
Although liquid sterilizing agents have been used for many years for sterilizing articles such as medical and dental instruments, packaging, and the like, and not withstanding research over many decades to solve the problems involved, the use of bulk liquid sterilants still suffers from a number of disadvantages. It is important that a disinfection process has the ability to kill all micro-organisms, and not merely one class, as is the case with many liquid agents. A major disadvantage of liquid sterilizing systems such as are currently used for sterilizing medical instruments is that they employ particularly hazardous chemicals the use of which are increasingly causing occupational health concerns around the world. Other disadvantages include long sterilization cycles, high materials costs, as well as costs associated with the time and energy required to subsequently remove liquid from an article and/or to dry it after sterilization and prior to use. In addition to requiring long treatment times and drying times, many liquid sterilants are corrosive or otherwise materials incompatible with endoscope construction materials. If excessive residual sterilizing agent is left on the instrument, there may be a risk of an anaphylactic reaction when the instrument is introduced into a body cavity, and to avoid that possibility residual sterilizing agent must be rinsed off. The use of rinse water in turn introduces a risk of infection but is a lesser evil than the possibility of cytotoxic reaction.
Also the requirement for rinse water imposes a need for a water supply and drainage system which is a major disadvantage in some locations. Moreover, the need for plumbing prevents such apparatus from being portable or easily relocated.
Gasses and Vaporized Sterilizing Agents, at Atmospheric Pressure or Above.
Traditionally, vapour sterilization of medical instruments was performed with steam (water vapour), usually in autoclaves at high temperature and pressure. More recently gases such as ethylene oxide have been used at temperatures around 55° C. (e.g. U.S. Pat. No. 4,410,492), but in view of both occupational health and environmental concerns, the use of such highly toxic gases has been largely discontinued in many countries and is being rapidly discontinued in others around the world.
The use of hydrogen peroxide vapours was pioneered in the packaging industry, where it has been practiced to “gasify” peroxides for use as a sterilizing agent. Hydrogen peroxide is considered harmless and non corrosive in comparison with ethylene oxide, chlorine, ozone and other gasses employed as sterilants. Hydrogen peroxide can be vaporized at atmospheric pressure by feeding droplets of 1-3 mm diameter onto a surface heated at 140-180° C. whereby the liquid is vaporized and then swept by a carrier gas to be directed at a surface to be sterilized (eg U.S. Pat. No. 4,797,255, Hatanaka) or by injecting the droplets into a pre-heated gas stream at above 140° C.
Hydrogen peroxide boils at 151.4° C. at 760 mm. FIG. 1 taken from U.S. Pat. No. 4,797,255 shows (curve A) how the boiling point at atmospheric pressure of a water/peroxide mixture changes with concentration and (curve B) how the gas composition changes. As is shown, pure water boils at 100° C. at atmospheric pressure. It is evident from FIG. 1 that the concentration of hydrogen peroxide in the vapour at below 100° C. is negligible at atmospheric pressure.
In peroxide vapour processes at atmospheric pressure, it is essential that the hydrogen peroxide vapour be kept at substantially above its Dew Point (i.e. below its Saturation Limit) throughout the entire process. Usually the transport air is injected at a significantly higher temperature (typically above 120° C.) and high transport gas flow rates are required. Such processes satisfy the requirements for aseptic packaging of food containers which can withstand such high temperatures. However many medical devices such as those employing fiber-optics, power tools, endoscopes etc are sensitive to heat and cannot be treated by vapour based processes subjected to such elevated temperatures, and therefore cannot be efficiently treated by hydrogen peroxide vapour at atmospheric pressure.
In 1979 Moore et al (U.S. Pat. No. 4,169,123) and Forstrom (U.S. Pat. No. 4,169,124) showed that hydrogen peroxide vapour could be an effective sterilant at below 80° C., given sufficient time. Spore strips were placed in a sealed package with a small amount of hydrogen peroxide solution and heated at above 60° C. for 24 hrs. By conducting the tests under vacuum, sterilization was reportedly achieved in 30 to 60 minutes, but sterilization could not be achieved in less than 6 hrs at atmospheric pressure at below 80° C.
To date, no gas or vapour systems using acceptable sterilants such as hydrogen peroxide have been sufficiently effective at atmospheric pressure and below 70° C. and to be commercialised for sterilization of medical instruments.
Gasses, Plasmas, and Vaporized Sterilizing Agents, at Reduced Pressure
Vacuum systems greatly facilitate the vaporization of sterilants at below 70° C. However, processes which operate at reduced pressure suffer from the general disadvantage that vacuum pumps, pressure vessels, vacuum seals and such like are required in the design of the equipment used. This reduces reliability and adds greatly to capital and maintenance costs, to energy and other running costs, as well as to cycle time. Commercially available vapour and plasma systems have a capital cost ranging from about US$75,000 for a 50 liter unit to about US$180,000 for a 200 liter unit. In such systems the combined time required for pumping down to the required vacuum, sterilization, and for subsequent drying of endoscopes is greatly in excess of 20 minutes. More importantly, the reduced pressure is not compatible with longer flexible lumens because of the sealed airspace between the lumen and the outer sheath of the flexible endoscope, and only short flexible endoscopes up to 30 cm in length can be treated with vacuum systems.
Most vapour based processes are conducted under reduced pressure, and of these, many employ deep vacuum. Following the work of Moore and Forstrom, a great deal of research was directed at vapour processes at reduced pressure. Vapour based sterilization processes conducted at reduced pressure are described in for example U.S. Pat. Nos. 4,642,165; 4,943,414*; 4,909,999, 4,965,145 5,173,258, 5,445,792*; 5,492,672*; 5,527508*; 5,556,607*; 5580530*; 5,733,503*; 5,869,000*; 5,906,794; 5,508,009; 5,804,139; 5,980,825*; 6,010,662; 6,030,579*; 6,068,815*; 6,589,481* 6,132,680*; 6,319,480*, 6,656,426* Of these several (marked with an asterisk) claim to have success in sterilizing lumens or mated surfaces, and demonstrate the difficulty that these systems represent. In sub atmospheric pressure vapour processes the best results have been achieved by starting with a concentrated 50% peroxide solution (unless otherwise specified all peroxide concentrations referred to herein are percentage by weight), reducing the pressure so as to selectively vaporise water, and thus concentrate the remaining peroxide. Water is removed through the vacuum pump. The vapour process needs to start with a high concentration of peroxide, since otherwise the time taken to vaporise and pump out the water is too long. The processes can't start with more concentrated peroxide because higher concentrations would represent a danger during transport and handling. Even at 50% concentration, hydrogen peroxide requires special packaging to protect users.
The most successful of the sub atmospheric pressure, low temperature, sterilization processes involve forming plasmas from the vapour, eg hydrogen peroxide plasmas. Plasma systems avoid the use of high temperatures by operating at sub-atmospheric pressures. Typically these systems operate at below 0.3 torr. While plasma has the advantage that the peroxide solution used may be in concentrations of as low as 1-6% by weight, in commercial practice the starting solution of peroxide is greater than 50% to reduce cycle time. This involves special precautions in shipping, storage and handling, since peroxide concentrations of 50% and above are corrosive to skin or severe irritants, while 35% and below are considered safer to handle. The necessity for sub atmospheric pressures is an enormous disadvantage since it greatly lengthens treatment time which is costly, and requires the use of high vacuum seals, vacuum pumps, pressure vessels, special valves etc. The requirement for vacuum equipment greatly reduces reliability and increases capital outlay and maintenance complexity. The plasma process is completely ineffective when even traces of moisture are present—The STERRAD™ plasma process is aborted if moisture is detected at ppm levels. The vast majority of medical instruments that are recommended for low temperature and chemical sterilization, for example endoscopes, face masks, respiratory hoses etc, are difficult to dry and especially so when they were pre-washed before sterilisation. An advantage of vacuum systems over liquid systems is that if condensation of the sterilant on the surface can be avoided, the sterilant can be removed without the need for rinsing.
Although by far the most costly processes to install and to operate, high vacuum processes have to date been the most effective for treating mated surfaces and lumens when applicable. However, this system is not applicable for long flexible endoscopes and can only be used with lumens up to about 25-30 cm in length.
Aerosol Processes.
The present process is an improved aerosol process. While aerosols have been used to sterilize packaging materials, to date it has not been possible to use aerosol systems to treat endoscopes and the like, and aerosols have not been adopted for sterilizing medical instruments. Although an aerosol of ethyl alcohol was proposed for disinfecting breathing apparatus as early as 1965 (Rosdahl GB 128245), that method is not suitable for sterilizing medical instruments, among other reasons because it does not solve the problem of mated surfaces, and because ethyl alcohol is not sporicidal. That method has not been adopted commercially despite being known for forty years.
Known peroxide nebulants in the prior art are in the form of a mist generally having a mean particle size upwards of about 5 microns. These have been employed to treat substrates that were fully exposed. Hoshino (U.S. Pat. No. 4,296,068) described a process for sterilizing food containers in which a mist of sterilizing particles, formed by spray nozzles, and having a diameter of about 20-50 microns, are entrained in air heated to 50-80° C. Kodera (U.S. Pat. No. 4,366,125) combines a similar process using 10 micron droplets in combination with UV radiation for treating sheet material. Blidshun describes a peroxide aerosol having particles of 2-5 microns.
In 1998 Kritzler et al. (PCT/AU99/00505) described a process in which a nebulant consisting of from 1% to 6% peroxide in combination with a surfactant is recycled through a nebulizer and through a sterilization chamber without introduction of an external carrier gas. Although that process was capable of achieving log 6 reduction of B. subtilis within about 60 seconds on exposed open surfaces, and despite the initial promise, subsequent work reported here revealed that the process was unable to achieve 6 log reductions of Stearothermophillus (ATCC 7953 as used in STERRAD® CycleSure biological indicator) in less than 30 minutes on open surfaces. Moreover, the time taken to treat (sterilize, dry, and remove residuals) occluded surfaces, mated surfaces or lumens was unacceptably longer. Therefore this process was uncompetitive with vapour systems for sterilizing lumens and mated surfaces. Moreover the process left high (3 mg/cm3) peroxide residuals on the surface, removal of which further added to processing time.
An advantage of hydrogen peroxide aerosol systems used to date is that the liquid nebulised had a concentration off 35% or less of hydrogen peroxide in the starting material which was considered safe to handle. However no aerosol sterilization systems developed to date have been satisfactory for sterilizing medical instruments and all have suffered from the following disadvantages:—
Firstly, aerosols have been unable to penetrate lumens and between mated surfaces of articles or into occluded areas of sterilization chamber in an acceptable time i.e. the time required for aerosols to achieve sterilization with lumens and mated surfaces was much longer than desired.
Secondly, the overall time required to achieve sterilization (i.e. a log 6 reduction in concentration of spores) at below 70° C. for some micro-organisms (for example resistant strains of Bacillus Stearothermophilus such as the ATCC 7953 strain), was much longer than desired.
Thirdly, when hydrogen peroxide is present in the form of small droplets (sprayed, ultrasonically nebulised, etc), the particles have a tendency to deposit as droplets on surfaces and the residual layer of peroxide is a potential problem. Medical instruments, food packaging and other disinfected items need to be stored dry to avoid re-contamination. Also surgical instruments must not contain residual peroxide at levels higher than 1 microgram/sq. cm. Eliminating residual peroxide is very difficult: It requires either washing which introduces the associated problems previously discussed in connection with liquid systems, prolonged periods of high temperature drying (which completely negate any advantages arising from fast kill times and low process temperature) or requires use of catalase or other chemical means to decompose peroxide (which still requires drying and which creates a series of problems with the residual chemicals left on instruments) or the use of vacuum.
In summary, it can be said that none of the sterilization methods currently available is entirely satisfactory for sterilizing medical instruments, and especially heat sensitive ones. More particularly, to date no process has been capable of (i) complete sterilisation of mated surfaces or lumens in under 20 minutes, (ii) at temperatures below 70° C., (iii) while yielding a dry ready-to-use product or surface (iv) without occupational health or environmental concerns. Moreover, the best commercially available processes suffer from major additional disadvantages. In the case of vapour and plasma systems pressure reduction is required, and commercial systems utilise hydrogen peroxide at concentrations of 50% or more as a starting material, requiring special packaging and handling. In the case of liquid systems a final rinse is required. Surveys of health professionals have repeatedly shown that the combination of achievement of criteria (i) to (iv) without either pressure reduction or rinsing would be highly desirable. Similar considerations apply to sterilization of other surfaces where pressure reduction and rinsing are often even less practicable.
Any discussion of the prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of common general knowledge in the field.